Mouse interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immuno/gene therapy

Yang,Xi; Tietje,Ashlee  H.; Yu,Xianzhong; Wei,Yanzhang

doi:10.3892/ijo.2016.3475

Mouse interleukin-12/FasTI: A novel bi-functional fusion protein for cancer immuno/gene therapy

Authors:
- Xi Yang
- Ashlee H. Tietje
- Xianzhong Yu
- Yanzhang Wei
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Affiliations: Department of Biological Sciences, Clemson University, Clemson, SC 29634, USA, Division of Science, Southern Wesleyan University, Central, SC 29634, USA
Published online on: April 7, 2016 https://doi.org/10.3892/ijo.2016.3475
Pages: 2381-2386

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Abstract

Whereas cancer immunotherapy with cytokines in recent research was demonstrated effective in activating immune response against tumor cells, one major obstacle with the use of these cytokines is their severe side effects when delivered systemically at high doses. Another challenge is that advanced tumor cells often evade immunosurveillance of the immune system as well as of the Fas-mediated apoptosis by various mechanisms. We report the design and preliminary evaluation of the antitumor activity of a novel fusion protein-mIL-12/FasTI, consisting of mouse interleukin-12 and the transmembrane and intracellular domains of mouse Fas. The fusion construct (pmIL-12/FasTI) was transfected into mouse lung carcinoma cell line TC-1. Stable cell clones expressing the fusion protein were established as assayed by RT-PCR and immunohistochemistry. ELISA and cell proliferation analyses demonstrated that NK cells were effectively activated by the fusion protein with increased IFN-γ production and cytotoxicity. Enhanced caspase-3 activity of the clones when co-cultured with NK cells indicated that apoptosis was induced through Fas/FasL signaling pathway. The preliminary results suggest a synergized anticancer activity of the fusion protein. It may represent a promising therapeutic agent for cancer treatment.

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